Regen Biopharma starts small molecule hit validation study on cancer stem cell target gene

These studies are expected to be completed within the next two months.

These studies are anticipated to produce purified recombinant protein and conduct an orthogonal assay to validate the results of High Throughput Screening of 170 compounds previously curated by the Company.

The Company is testing a list of 170 hit compounds out of 300,000 compounds that had been initially tested. A hit is a compound that gives a positive signal in a screening assay that is used to indicate binding of a compound to the region of the protein that regulates the protein’s function.

The desired outcome is to find a "hit" that will bind to and turn off the cancer stem cell target gene that the Company is working on, and hence allow the transformation of a cancer stem cell into a normal cell.

The 170 compound short list was generated by ranking the top hits in order of priority based on medicinal chemistry desirability and on exclusion of Pan Assay Interference (PAINS) compounds.

An orthogonal assay uses a different methodology than methodology used in the initial screen to test the compounds ability to bind to the target. While the luciferase reporter assay methodology was used to carry out the high-throughput screen, to eliminate the biases that are introduced by the testing method, the Company will carry out validation of the hits using thermodynamic drug discovery methods.

Validation of the hits will allow the Company to identify the most viable candidates for hit to lead discovery. Hit to lead is a stage in early drug discovery where small molecule hits from a high throughput screen are evaluated and undergo limited optimization to identify promising lead compounds

Molecular Therapeutics director Christine Ichim said: "We wish to develop the best possible small molecule drug to act as a synthetic agonist to our cancer stem cell nuclear receptor target, so while we did have initial results showing that some nuclear receptors ligands could also act as a small molecular ligand for our cancer stem cell gene target we wanted to develop the best product possible so we made a strategic decision to survey a much broader chemical space and pursue hits from a high throughput screening approach.

"High throughput screening allows the survey of a very broad array of chemical structures, giving us an unbiased look at what could bind best to our target."